Monday, May 30, 2011

"Sticky" LDL

The Internet is awash with stories announcing the discovery of a new "sticky" LDL (low-density lipoprotein) molecule that is much more deadly than the regular LDL. This new LDL is called MGmin-LDL.

Most of the stories simply reprint the press release used by Science Daily and EurekAlert and other popular science-news alerting services. These tell you that the new form of LDL is glycated and it turns LDL into small, dense LDL, the kind that is more easily taken up by the arterial wall to form plaque.

Interestingly, metformin seems to block the formation of MGmin-LDL.

But what exactly is MGmin-LDL?

The MG stands for methylglyoxal, which is a highly reactive side product of glycolysis (the aerobic metabolism of glucose). MG reacts with proteins and is one way cells produce AGEs, or advanced glycation end products, which are glycated proteins that cause a lot of the side effects associated with diabetes.

MG is known to cause AGEs in a lot of proteins, including enzymes and DNA transcription factors, and has even been implicated as a cause of insulin resistance. MG has also been used as a marker of oxidative stress. We know that glycated proteins are not effective. Glycation of serum albumin (not necessarily by MG) seems to decrease insulin secretion. Glycation of LDL reduces its uptake by the LDL receptor. And so forth.

The higher your blood glucose (BG) levels, the more MG you make and the more glycation of protein occurs. One study showed that MG levels reflected the level of postprandial BG levels and suggested that high postprandial levels are as important as hemoglobin A1c levels when it comes to causing complications.

In fact, the idea that MG reacts with LDL is not new. It was shown in 1998, and possible even earlier, that MG reacts with LDL. However, each new research project adds new information, and the current one emphasized the atherogenicity of the MG-LDL complex.

min in the MGmin-LDL stands for minimally modified, meaning that they didn't carry out the reactions to such an extent that the product was not physiological. They modified it so that it was present in concentrations they thought would actually occur in a human.

It's interesting that the popular, and generic, drug metformin reduces the level of MGmin-LDL. It may do this by blocking the formation of MG.

Because MG is formed as a byproduct of glycolysis, the more glucose that goes through the glycolytic pathway, the more MG you'll be apt to make. But glucose not only source of MG. Other compounds, including ketones, can also be broken down into MG.

Hence, just to be on the safe side, the best way to reduce the levels of MG might be simply to eat less food of all kinds. But we have to eat something, so eating less of the glucose-forming foods would most likely be the most effective in reducing the levels of MG. We know that high BG levels increase glycation of all kinds of proteins, as illustrated above, whether through MG or other mechanisms. Some of these proteins are needed to keep our bodies in top working order. Glycating them means they can't do their job.

It's hard to give up the carby foods we love. But to me, it doesn't make sense to risk getting complications just for the temporary pleasure of eating rice or toast and jam.